Many pharmaceutically active substances are presented for oral administration in the form of tablets, pills or capsules. The tablet, pill or capsule generally has to be swallowed with water so that the pharmaceutically active substance can be absorbed via the gastro intestinal tract. For some patients swallowing the tablet, pill or capsule is difficult or impossible and this is particularly the case for paediatric patients and geriatric patients. A similar difficulty is often encountered when trying to administer tablets to non-human animals which may be uncooperative in taking tablets, pills or capsules.
Oral solid pharmaceutical dosage forms which rapidly disintegrate in the mouth and methods for their preparation have been proposed in GB-A-1548022 and GB-A-2111423. The solid dosage forms as disclosed comprise an open matrix network carrying the pharmaceutically active substance, the open matrix comprising a water-soluble or water-dispersible carrier material which is inert towards the pharmaceutically active substance. The solid dosage forms are prepared by the sublimation or removal of solvent from a solution or suspension comprising the pharmaceutically active substance and the carrier material. Sublimation or removal of solvent is preferably carried out by freeze drying.
Other methods for the preparation of oral solid pharmaceutical dosage forms which rapidly disintegrate in the mouth are disclosed in EP-A-0627218, U.S. Pat. No. 4,855,326, U.S. Pat. No. 5,039,540, U.S. Pat. No. 5,079,018, U.S. Pat. No. 5,120,549, U.S. Pat. No. 5,298,261, U.S. Pat. No. 5,330,763, U.S. Pat. No. 5,587,180, WO 91/04757 (PCT/US90/05206), WO 93/12769 (PCT/JP93/01631) and PCT/US93/12566.
The solid dosage forms which are produced by these various methods rapidly disintegrate on being placed in the mouth of the patient, thereby delivering the desired dose of the pharmaceutically active substance.
Although the solid dosage forms as described above overcome the problem of swallowing tablets, pills or capsules, the patient will taste the pharmaceutically active substrate as the dosage form disintegrates. For some pharmaceutically active substances the taste, if slightly unpleasant, can be rendered acceptable by the use of sweetening agents or flavouring agents which mask the taste. However, for some pharmaceutically active substances an unpalatable product will still be produced, despite the use of sweetening agents and flavouring agents, which decreases patient compliance.
In WO-A-96/13252, we have described a process for the preparation of an oral solid rapidly disintegrating dosage form of a pharmaceutically active substance having an unacceptable taste, the process involving presenting the pharmaceutically active substance in the network of carrier material in a form which is less soluble in water and more palatable than the form with the unacceptable taste.
Whilst the use of lipids to tastemask or modify drug release has been proposed in the prior art, for example WO-A-94/05260 and WO-A-94/25006, the compositions disclosed therein are liquid dosage forms which include high levels of sweeteners, such as sucrose. In these liquid dosage forms the lipid coats the drug particles to form a physical barrier to delay release of the drug. Such compositions cannot be formed into freeze dried dosage forms since release of the drug would occur during the aqueous suspension stage.
EP-A-0631787 describes the use of acidic phospholipids for the suppression of bitter taste in foods, toiletries or in pharmaceutical compositions such as capsules, granules, liquids or syrups.